Paliwal Swati, Chaudhary Kajal, Agarwal Uma, Tonk Rajiv Kumar
Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, Pushp ViharSector-3, M-B Road, New Delhi, 110017, India.
Faculty of Pharmacy, Ram-Eesh Institute of Vocational and Technical Education, Greater Noida, India.
Curr Microbiol. 2025 Aug 20;82(10):465. doi: 10.1007/s00284-025-04455-z.
Nafithromycin (WCK 4873), is India's first approved macrolide antibiotic by DCGI(Drug Controller General of India), represents a significant advancement in combating antimicrobial resistance (AMR) and multidrug-resistant (MDR) pathogens. After three decades of research and development, supported by BIRAC, Wockhardt Ltd. successfully developed this innovative lactone- ketolide antibiotic which demonstrates superior efficacy against respiratory pathogens, particularly drug-resistant Streptococcus pneumoniae. Its unique structural modifications at the C-3 position and enhanced side chain configurations improve its pharmacological profile compared to previous generation macrolides. Nafithromycin binds to both domains II and V of 23 s rRna, thereby circumventing the resistance mechanisms which impacts older macrolide due to their single target binding. Owing to dual binding of nafithromycin, it is more potent than the older macrolides. Additionally, nafithromycin exhibits immunomodulatory effects in acute lung injury models, suggesting potential therapeutic benefits beyond its antimicrobial activity. Moreover, Phase I and II trials demonstrate its safety and tolerability, with minimal drug-drug interactions due to reduced CYP3A4/5 inhibition. Phase III results show that nafithromycin is effective against a wide variety of respiratory infections as well as intracellular atypical pathogens which can be difficult to treat other ways. No significant AEs were encountered. In this comprehensive review, the adverse effects of other antibiotics are examined, along with the benefits of nafithromycin over other medications, its development, mechanism of action, structure-activity relationships, clinical efficacy, drug delivery strategies via various routes to overcome antimicrobial resistance, strategies to combat antimicrobial resistance, and future perspectives in addressing the global antimicrobial resistance challenges.
萘夫西林（WCK 4873）是印度药品总局（DCGI）批准的印度首款大环内酯类抗生素，在对抗抗菌药物耐药性（AMR）和多重耐药（MDR）病原体方面取得了重大进展。在生物技术产业研究援助理事会（BIRAC）的支持下，经过三十年的研发，沃克哈特有限公司成功开发出这种创新的内酯 - 酮内酯抗生素，它对呼吸道病原体，特别是耐药肺炎链球菌具有卓越的疗效。与前代大环内酯类药物相比，其在C - 3位独特的结构修饰和增强的侧链构型改善了其药理学特性。萘夫西林与23 s rRna的结构域II和V都结合，从而规避了由于单一靶点结合而影响旧大环内酯类药物的耐药机制。由于萘夫西林的双重结合，它比旧的大环内酯类药物更有效。此外，萘夫西林在急性肺损伤模型中表现出免疫调节作用，表明其潜在治疗益处超出了抗菌活性。而且，I期和II期试验证明了其安全性和耐受性，由于对CYP3A4/5的抑制作用降低，药物 - 药物相互作用最小。III期结果表明，萘夫西林对多种呼吸道感染以及其他方式难以治疗的细胞内非典型病原体有效。未发现明显的不良事件。在这篇全面综述中，研究了其他抗生素的不良反应，以及萘夫西林相对于其他药物的益处、其研发、作用机制、构效关系、临床疗效、通过各种途径克服抗菌药物耐药性的药物递送策略、对抗抗菌药物耐药性的策略以及应对全球抗菌药物耐药性挑战的未来展望。
